Medical Biochemistry Lecture 8: Acid-base Imbalance PDF

MLS2109: Medical Biochemistry Lecture 8: Acid-base imbalance Prof. Lifoter Kenneth Navti Outline Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory alkalosis 2 1. Acid-base imbalance Acid-Base imbalance can manifest as acidosis and alk...

MLS2109: Medical Biochemistry Lecture 8: Acid-base imbalance Prof. Lifoter Kenneth Navti Outline Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory alkalosis 2 1. Acid-base imbalance Acid-Base imbalance can manifest as acidosis and alkalosis. Acidosis: Which can be; Metabolic acidosis and Respiratory acidosis. Alkalosis: Which can be; Metabolic alkalosis and Respiratory alkalosis. All of the above may be in compensated phase and uncompensated phase. 3 2. Metabolic acidosis Also called as primary alkali deficit. It is the commonest disturbance of acid-base balance observed clinically. It is caused when there is a reduction in the plasma HCO3– ↓ (B. HCO3 ↓) with either no or little change in the H2CO3 fraction. Mechanisms: If primary deficit of HCO3– occurs the ratio [HCO3–] / [H2CO3] = 20/1, is decreased, i.e. pH is decreased resulting in metabolic acidosis (primary bicarbonate deficit). 4 2.1. Primary compensatory mechanism The respiratory centre is stimulated by acidosis causing deep and rapid (Kausmaul) breathing. This increased ventilation will result in CO2 loss and reduction in [H2CO3] ↓ (carbonic acid). As a result, the ratio of [HCO3–] / [H2CO3] is restored towards 20:1, as levels of both in blood are reduced. However, increased ventilation causes reduction in pCO2 ↓, which in turn depresses the respiratory centre. 5 2.1. Primary compensatory mechanism Thus, two opposing forces: Acidosis stimulating respiratory centre and Low pCO2 depressing respiratory centre, are set against each other, and respiratory compensation is only partial. 6 2.1. Primary compensatory mechanism During the early stages of alkali deficit, therefore, the organism is in a state of compensated acidosis. But as the condition progresses and if the treatment is not instituted, the alkali deficit becomes more pronounced, the primary compensatory mechanism fails and the condition becomes one of uncompensated acidosis with an increase in H+ ion concentration in blood. 7 2.2. Secondary compensatory mechanism Renal mechanisms attempt to correct the disturbances as follows: By conserving cations By increasing NH3 formation ↑ H+ excretion compared to K+ excretion in distal tubule, and HCO3– reabsorption 8 2.3. Biochemical characteristics Uncompensated: If uncompensated, it is characterized biochemically in plasma or blood as follows: Disproportionate decrease in [HCO3–] ↓ Decrease in [H2CO3] ↓ and pCO2↓ Decrease in total CO2 content [HCO3–] + [H2CO3] Decrease in [HCO3–] : [H2CO3] ratio ↓ Decrease in pH ↓ 9 2.3. Biochemical characteristics Fully compensated: If fully compensated the CO2 content is low, but the decrease in [HCO3–] and [H2CO3] is proportionate, the [HCO3–] : [H2CO3] ratio and pH remain within normal limits. 10 2.3. Biochemical characteristics Urinary findings: pH: acidic Increased excretion of NH4Cl and NaH2PO4 Increase in titratable acidity 11 2.4. Causes Abnormal increase in anions other than HCO3- (acid gain) Endogenous production of acid ions when excessive Diabetic acidosis Starvation High fever Violent exercise Lactic acidosis due to other causes like shock and haemorrhage Ingestion of acidic salts Renal insufficiency of acids normally produced Abnormal loss of HCO3-, e.g. in severe diarrhea 12 3. Respiratory acidosis It is also called as “primary [H2CO3] carbonic acid excess’’. The underlying abnormality here is increase in H2CO3 ↑ in the blood, which follows decreased elimination of CO2 (pCO2 ↑) in the pulmonary alveoli. This may result from: Breathing air containing abnormally high percentage of CO2, and Conditions in which elimination of CO2 through lungs is retarded. 13 3.1. Mechanism If excretion of CO2 through lungs is impaired (e.g. emphysema or depression of respiratory centre), more CO2 will accumulate in blood, resulting in excess H2CO3 formation [H2CO3] ↑. This results in lowering the ratio of [HCO3–]/[H2CO3], resulting lowering in pH ↓ and is described as “Respiratory acidosis” (carbonic acid excess). Compensatory mechanism: In this condition, the respiratory mechanism becomes secondary and renal mechanism becomes of prime importance. 14 3.1.1. Respiratory mechanism Increased stimulation to respiratory centre (RC) by the increased CO2 tension (pCO2↑) results in increased depth and rate of respiration with consequent increased ventilation. This mechanism becomes secondary in importance as the defect may be with the RC, its depression/or some pathology in the Lungs. As a result this compensatory mechanism becomes less effective. 15 3.1.2. Renal mechanism It is of prime importance. More HCO3– are reabsorbed from tubules in response to raised pCO2 in blood and ratio of [HCO3–]/[H2CO3] is restored towards 20:1 as the levels of both in blood are increased. 16 3.2. Biochemical characteristics If uncompensated, it is characterized biochemically (plasma or blood) as follows: Disproportionate increase in [H2CO3] ↑ (pCO2) ↑ Increase in [HCO3–] ↑ Increase in total CO2 content ↑ Decrease in [HCO3–] : [H2CO3] ratio ↓ Decrease in pH ↓ 17 3.2. Biochemical characteristics If fully compensated; The CO2 content is high, but the increase in [H2CO3] and [HCO3–] are proportionate, the [HCO3–] : [H2CO3] ratio and pH remaining within normal limits. 18 3.2. Biochemical characteristics Urinary findings The urinary NH3 ↑ and titratable acidity are increased ↑ (if kidneys are functioning normally). 19 3.3. Causes Conditions in which there is depression or suppression of respiration Damage to CNS: Brain damage: Trauma, inflammation, or compression and convulsive disorders. Drug poisoning: Like morphine and barbiturates. Excessive anaesthesia. Loss of “ventilatory functions” due to increased intrathoracic pressure or loss of elasticity. Tension cyst/and tension pneumothorax, pulmonary tumors. 20 3.3. Causes Conditions in which there is an obstacle to the escape of CO2 from the alveoli: Obstruction to respiratory tract – Laryngeal obstruction – Asthma. Rebreathing from a closed space. 21 4. Metabolic alkalosis Also called as primary alkali excess. This condition results from an absolute or relative increase in [HCO3–]. Primary alkali excess or increase in the “alkali reserve” is the most frequent cause of clinically observed alkalosis. 22 4.1. Mechanism Excess of HCO3– accumulation (soluble alkali ingestion) causes an increase in the ratio of [HCO3–]/ [H2CO3] (i.e. pH is increased ↑) and it is known as “Metabolic alkalosis” (“bicarbonate excess”). The respiratory centre (RC) is inhibited by alkalosis causing shallow, irregular breathing. This reduced ventilation will result in CO2 retention and increases in carbonic acid level [H2CO3] ↑. The ratio of [HCO3–]/[H2CO3] will be restored towards 20:1 as the levels of both in blood are increased. However, decreased ventilation raises pCO2, which tends to stimulate the RC. 23 4.1.1. Opposing forces Again, opposing forces Alkalosis depressing, and Raised pCO2 stimulating the RC are working simultaneously and the respiratory compensation is incomplete 24 4.1.2. Renal mechanisms Increases the excretion of: Cations ↑ HCO3– ↑ (replacing Cl– in urine). Both are due to decrease H+-Na+ exchange. K+ excretion increases in the distal tubules instead of H+. There is reduced NH3 ↓ formation and excretion of non-volatile acids, viz. lactic acid and ketoacids. 25 4.1.3. Compensatory mechanisms The following compensatory mechanisms operate: Decreased pulmonary respiration ↓ Increased alkali excretion ↑ Decreased acid excretion ↓ Decreased NH3 formation ↓ Retention of acid metabolites 26 4.1.4. Urinary findings Urinary acidity decreases ↓ and decrease NH3 formation. Decrease in titratable acidity ↓. 27 4.1.5. Other biochemical changes Hypokalaemia: Increased excretion of K+ from distal tubules can produce K+ depletion (decrease serum K+ concentration—hypokalaemia). Kidney damage: Mainly degenerative changes in the tubules (nephrosis) occurs frequently with oliguria and N2-retention. Ketosis and ketonuria: Ketosis and ketonuria may occur frequently in alkalosis, due to excessive vomiting because of inadequate carbohydrates intake. 28 4.2. Biochemical characteristics If uncompensated, it is characterized biochemically (plasma or blood) as follows: Disproportionate increase in [HCO3–] ↑ Increase in [H2CO3] ↑, pCO2 ↑ Increase in total CO2 content Increase in [HCO3–]:[H2CO3] ratio ↑ Increase in pH ↑ 29 4.2. Biochemical characteristics If fully compensated the CO2 content is high, but the increase in [HCO3–] and [H2CO3] are proportionate, and the [HCO3–] : [H2CO3] ratio and pH remaining within normal limits. Urinary findings: The urinary NH3↓ and titratable acidity ↓, both are decreased (if kidneys are functioning normally). 30 4.3. Causes Excessive loss of HCl from stomach: The loss of excessive quantities of HCl from the stomach is encountered most frequently in individuals with: Pyloric obstruction, High intestinal obstruction, Sometimes in patients with generalised peritonitis. As a result of the loss of Cl– ions from the blood there is present in the body an excess of base, chiefly Na+ and K+, which is retained in the form of bicarbonate. In this way, a neutral salt (NaCl) is replaced by an alkaline salt (NaHCO3). 31 4.3. Causes Alkali administration: Excessive intake of bases like NaHCO3, Na and K acetates, lactates or citrates. Lactates and citrates are converted into HCO3–. Potassium deficiency: Produces alkalosis 32 5. Respiratory alkalosis Also called as primary H2CO3 deficit. This condition occurs when there is a decrease in [H2CO3] ↓ fraction with no corresponding change in HCO3– in plasma. Excessive quantities of CO2 may be washed out of the blood by hyperventilation. 33 5.1. Mechanism Increased loss of CO2 (due to hyperventilation), results in diminution of [H2CO3] ↓. The ratio of [HCO3–]/[H2CO3] is increased ↑ (i.e. pH is increased) and is termed “respiratory alkalosis” (carbonic acid deficit). In this condition, due to increased CO2 loss, pCO2 is low, which leads to less H+ –Na exchange and less bicarbonate is reabsorbed (i.e. more HCO3– is excreted) by the renal tubules and the ratio of [HCO3–]/[H2CO3] returns towards normal, i.e. 20:1, as levels of both in blood are decreased. Alkalosis and low pCO2 depress respiratory centre and excretion of CO2 is reduced. 34 5.1.1. Compensatory mechanisms In this condition, main compensatory mechanism is ‘renal’. Excretion of alkali in the form of HCO3– Decreased excretion of acid Decreased excretion of NH3 in the urine Retention of Cl– in the blood. In view of the pathogenesis of this condition, the task of compensating for this defect falls on the kidneys. Other features are similar to metabolic alkalosis 35 5.2. Biochemical characteristics If uncompensated, it is characterized biochemically (plasma or blood) as follows: Disproportionate decrease in [H2CO3]↓ and pCO2 ↓ Decrease in [HCO3–] ↓ Decrease in CO2 content ↓ Increase in [HCO3–] : [H2CO3] ratio ↑ Increase in pH ↑ 36 5.2. Biochemical characteristics If fully compensated, the CO2 content is low, but the decrease in [HCO3–] and [H2CO3] is proportionate, the [HCO3–] : [H2CO3] ratio and pH remaining within normal limits Urinary findings: The urinary NH3 ↓ and titratable acidity ↓ are both decreased (if kidneys are functioning normally). 37 5.3. Causes Stimulation of Respiratory Centre (RC) In CNS diseases, e.g. meningitis, encephalitis. Alkalosis due to hyperventilation has been observed in some cases of meningitis/encephalitis, etc. manifesting hyperpnoea, over prolonged periods of time. Salicylate poisoning: Large doses of salicylates, such as are sometimes given in the treatment of acute rheumatic fever, produce stimulation of Respiratory centre (RC) with consequent hyperventilation and tendency towards alkalosis. Hyperpyrexia: Hyperventilation may occur as a result of the increased respiratory rate associated with increase in body temperature. 38 Thank you 39